Aromatase Inhibitor Associated Musculoskeletal Symptoms (AIMSS), Breast Cancer, Pain Alleviation
Conditions
Brief summary
The goal of this clinical trial is to learn whether transcutaneous auricular vagus nerve stimulation, also called taVNS, can help relieve aromatase inhibitor-related joint and muscle pain in adult women with hormone receptor-positive breast cancer. The main questions this study aims to answer are: 1. Does taVNS reduce pain caused by aromatase inhibitor treatment? 2. Does taVNS improve quality of life, mood symptoms, and the need for pain medicine? 3. What side effects or medical problems occur during treatment? Researchers will compare active taVNS with sham stimulation. Participants in both groups will receive mild electrical stimulation around the ear, but the sham stimulation will be applied to an area not expected to activate the vagus nerve. Participants will: 1. Be randomly assigned to active taVNS or sham stimulation 2. Receive one 30-minute treatment session every day for 28 days 3. Complete pain, mood, and quality-of-life questionnaires before treatment, after treatment, and during follow-up 4. Report pain medicine use and any side effects 5. Provide small blood samples to measure inflammatory markers, T-cell profiles, and tumor markers Participants will be followed for up to 6 months after treatment. For some participants who do not have enough pain relief after taVNS, an optional second-stage study may be offered. In this stage, participants may receive low-dose interleukin-2, also called IL-2, by injection every other day for 2 weeks.
Interventions
DEVICEtranscutaneous auricular vagus nerve stimulation
Electrodes will be placed on specific areas of the participant's left external ear that are mainly innervated by the auricular branch of the vagus nerve. The electrodes will be connected to an electrical stimulation device, and stimulation will be delivered at tolerable intensity using preset study parameters. Treatment will be given once daily for 28 consecutive days.
DEVICEsham stimulation
Compared with transcutaneous auricular vagus nerve stimulation group, electrodes will be placed on different areas of the participant's left external ear that are not innervated by the auricular branch of the vagus nerve. The electrodes will be connected to an electrical stimulation device, and stimulation will be delivered at tolerable intensity using preset study parameters. Treatment will be given once daily for 28 consecutive days.
Sponsors
Peking University People's Hospital
National Natural Science Foundation of China
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Outcomes Assessor)
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Female participants aged over 18 years; 2. Patients with pathologically confirmed stage I-III primary breast cancer; 3. Patients who have recovered from systemic symptoms related to surgery, radiotherapy, or chemotherapy; 4. Patients with estrogen receptor- and/or progesterone receptor-positive breast cancer who are receiving aromatase inhibitor therapy and have aromatase inhibitor-related musculoskeletal pain, with a score greater than 3 on the Worst Pain item of the Brief Pain Inventory (BPI-WP); 5. Patients who have received aromatase inhibitor therapy for more than 30 days and are expected to continue treatment for more than 1 year; 6. Patients who voluntarily agree to participate in this study and sign the informed consent form. For participants receiving combined IL-2 treatment, the following additional criterion applies: 7. Pain relief rate of less than 50% after taVNS treatment and a lower peripheral blood Treg count than before treatment.
Exclusion criteria
1. Patients with advanced breast cancer; 2. Patients with other significant organ dysfunction, such as major cardiovascular disease, diabetes mellitus, or hyperthyroidism; 3. Patients with other cancers; 4. Patients with a history of fracture or surgery around the painful joint area within the past 6 months; 5. Patients currently receiving corticosteroids or opioid therapy; 6. Patients with contraindications to vagus nerve stimulation; 7. Patients who are unable to communicate normally, such as those with cognitive impairment or hearing impairment; 8. Patients who have participated in another clinical trial within the past 1 month. For participants receiving combined IL-2 treatment, the following additional
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| The pain relief rate of patients at the end of the 4-week treatment period | From enrollment to the end of treatment at 4 weeks. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Pain relief rate at follow-up | At 1, 2, 3, and 6 months after completion of treatment. | — |
| Dosage of analgesic drugs | At 1, 2, 3, and 6 months after completion of treatment. | — |
| Depression scores | At 1, 2, 3, and 6 months after completion of treatment. | PHQ-9 is used to measure depression. PHQ-9 ( unabbreviated scale title: Patient Health Questionnaire-9) Minimum Value: 0 Maximum Value: 27 Score Interpretation: Higher scores mean a WORSE outcome. Details:The PHQ-9 is a screening tool for depression. A higher score indicates more severe depressive symptoms. Generally, scores are interpreted as follows: 0-4 (Minimal), 5-9 (Mild), 10-14 (Moderate), 15-19 (Moderately Severe), and 20-27 (Severe) depression. |
| Anxiety scores | At 1, 2, 3, and 6 months after completion of treatment. | GAD-7 is used to measure anxiety. GAD-7 (unabbreviated scale title: Generalized Anxiety Disorder-7) Minimum Value: 0 Maximum Value: 21 Score Interpretation: Higher scores mean a WORSE outcome. Details:The GAD-7 measures the severity of generalized anxiety disorder. A higher score reflects more frequent and severe anxiety symptoms. Typical interpretations are: 0-4 (Minimal), 5-9 (Mild), 10-14 (Moderate), and 15-21 (Severe) anxiety. |
| Quality of life score | At 1, 2, 3, and 6 months after completion of treatment. | Quality of life assessed by the EuroQol 5-Dimension 5-Level questionnaire and EuroQol Visual Analogue Scale Description: Quality of life will be assessed using the EuroQol 5-Dimension 5-Level questionnaire (EQ-5D-5L) and the EuroQol Visual Analogue Scale (EQ VAS). For the EQ-5D-5L descriptive system, scores range from 5 to 25, with higher scores indicating worse health status. For the EQ VAS, scores range from 0 to 100, with higher scores indicating better self-rated health status. |
| Plasma inflammatory marker levels | Baseline, immediately after completion of treatment, and 6 months after completion of treatment. | — |
| The proportion of T cells in the blood | Baseline, immediately after completion of treatment, and 6 months after completion of treatment. | — |
| The count of T cells in the blood | Baseline, immediately after completion of treatment, and 6 months after completion of treatment. | — |
Countries
China
Contacts
CONTACTYi Feng, M.D
CONTACTPei Li, M.D
Outcome results
None listed